Mad cow vaccine hunt both urgent, unprecedented
Fri Jan 2,10:30 AM ET Add Top Stories - Chicago Tribune to My Yahoo!
By Jeremy Manier Tribune staff reporter
The quest for a vaccine that might protect against mad cow disease--an effort newly urgent now that a case has surfaced in the U.S.--is a huge scientific challenge unlike any other that infectious disease researchers have encountered.
The crux of the problem is the cause of the illness: inanimate proteins called prions that are fundamentally different from the viruses and bacteria that cause other diseases and demand a different line of attack.
Infectious prions are virtually identical to normal proteins found throughout the body, making it difficult to make treatments or vaccines that target only bad proteins.
"The problem is that this isn't a typical infection," said Jim Mastrianni, a prion researcher at the University of Chicago. "Normally treatments for infections basically disrupt the cell wall or outer membrane of an organism. Here you have just a protein, one that's resistant to acids, heat, just about anything."
Such difficulties have led scientists to consider unusual and even radical solutions, including genetically modifying cows so they can no longer contract the disease or pass it on.
Few experts believe the threat from mad cow disease, found recently in one cow in Washington state, is great enough to warrant such an extreme step, much less universal vaccination of people or animals.
But a vaccine could help contain outbreaks, and doctors are hopeful that some treatment can be developed for people who contract the dangerous human variant of the disease.
Meanwhile, work on prion sicknesses is slowly shedding light on that poorly understood and incurable form of infection. It may also aid the treatment of more common disorders such as Alzheimer's disease (news - web sites).
Much of disease a mystery
So little is known about prion diseases such as bovine spongiform encephalopathy, also called BSE (news - web sites) or mad cow disease, that scientists still do not understand what function the wayward proteins normally play in the body. Even the main hallmark of the illness--an eating away of brain tissue, leading to spongy gaps, delirium and ultimately death--remains a mystery.
"In the disease you get massive neuronal loss in the brain, but nobody really understands why that happens," said Anthony Williamson, a prion expert at Scripps Research Institute in La Jolla, Calif.
What experts do know about prion diseases suggests that any therapies or vaccines--for people or animals--are a long way off.
Most vaccines for other illnesses stimulate the body's natural immune defenses against whatever germ has intruded. That may be impossible with BSE or its human form, a variety of Creutzfeldt-Jakob disease (news - web sites), because the proteins that cause the disease appear to the immune system as normal compounds, not foreign invaders.
The only differences between the bad proteins and their normal counterparts are their shapes, which the immune system can't discern. To function properly, proteins must fold into precise shapes. Experts believe that folding goes awry in prions, which then serve as templates to transform normal proteins into deformed ones. The bad proteins stick together in the brain and form fibers, which are thought to play some role in the disease.
Many researchers, including Mastrianni and Williamson, have been working on creating artificial antibodies that can tell the difference between prions and normal proteins and make chemical bonds with one or the other. Last summer, a team from the University of Toronto published a study showing that certain antibodies can lock onto abnormal proteins.
That work has been helped by growing knowledge of how prions bond with normal proteins and alter their shapes.
"The hope is that by stopping that binding process you can hold off the disease," Mastrianni said.
No one knows how to make the body create such antibodies on its own. But it's possible that antibodies made in the lab could be used for what researchers call "passive immunization." Injecting large amounts of the antibody could plug up the chemical sites where normal and abnormal proteins latch onto each other, thus preventing a prion infection from taking hold.
Approach like Alzheimer's
A different approach would be to treat the disease at a later stage, by keeping prions from forming the fibers thought to play a role in brain damage. That's similar to treatments being developed for Alzheimer's disease, which also appears linked to an abnormal clumping of proteins in the brain.
"It's even conceivable that drugs that work for one disease would work in the other, by blocking protein aggregation," said Bruce Chesebro, chief of the viral diseases laboratory at Rocky Mountain Laboratories in Montana.
Although scientists don't understand how protein clumping leads to mad cow disease, that shouldn't hinder research on how to disrupt the process.
"You don't have to know the cause to be able to treat the disease," said Chesebro, whose lab is part of the National Institutes of Health (news - web sites). "There's a lot we still don't understand about the causes of cancer. But through massive, random screening of drugs in the lab, it changed from a situation that was hopeless in the1940s to one where certain cancers can be cured with chemotherapy."
The variant of Creutzfeldt-Jakob disease linked to the consumption of prion-infected beef is rare but deadly. The illness has killed at least 137 people in the United Kingdom, where mad cow disease first spread in the 1980s, but no human cases have been traced to American beef.
Researchers also are looking for ways of halting the spread of a related form of spongiform encephalopathy in deer and elk in the U.S. That outbreak has affected wild animals in at least eight states and first appeared in Illinois in late 2002.
One drastic option if mad cow disease ever became a major concern would be to genetically engineer cattle so they no longer produce the normal proteins that prions recruit to make bad proteins and cause disease.
"Strictly from a prion disease perspective, that would definitely prevent the problem," said Williamson of the Scripps Institute.
The approach carries many uncertainties, even apart from the public's leeriness of genetically modified foods.
Researchers have created transgenic mice that lack genes for the normal proteins. Those animals survive and have no obvious health problems--but that fact has only added to the confusion about what role the proteins play. Most experts believe the body must have built-in redundancy that protects animals that lack the protein.
But no one knows for sure, and researchers say it would be foolhardy to make such transgenic cattle on a large scale before it's clear how the protein works. Chesebro said researchers in Britain and the U.S. already are laying the groundwork for such transgenic experiments in cattle and in sheep, which also are susceptible to prion diseases.
"It's probably going to be tried, and people will see if it can be done," Chesebro said
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